American Indians/Alaska Natives [AIAN] and other Indigenous Populations (IP) of the Americas experience persistent and dire health disparities related to substance abuse and addictions (SAA). Despite such glaring disparities, there is a paucity of culturally grounded research addressing their biomedical and socio-behavioral health concerns. A strong network of highly trained Indigenous scholars dedicated to culturally relevant SAA research would contribute to ameliorating SAA-related health disparities among IP. This new application, in response to PAR-19-246, ?Providing Research Education Experiences to Enhance Diversity in the Next Generation of Substance Abuse and Addiction Scientists? will develop the INSPIRE: An Indigenous Substance abuse and addictions Prevention Interdisciplinary Research Education program. INSPIRE will develop a cadre of culturally grounded AIAN substance abuse and addictions scholars capable of serving as principal investigators on extramurally funded SAA-related prevention and disparities studies; as well as to develop a cohort of qualified doctoral and post-doctoral trainees from IP who have been historically underrepresented in biomedical and socio-behavioral research careers dedicated to furthering their studies or careers in SAA research with IP. The INSPIRE program is based on the success of our Indigenous Substance abuse and Medicines Research Training (ISMART) NIDA Contract program (HHSN271201700716P), one of two AIAN- focused substance abuse and addictions research development programs in the country. INSPIRE will provide a 24-month substance abuse and addictions research mentoring program to 20 qualified scholars (5 doctoral, 15 postdoctoral/early career) primarily from AIAN and other Indigenous populations (e.g., Native Hawaiians and Pacific Islanders) who are currently conducting research with AIAN/IP populations. INSPIRE mentees will undergo a structured, intensive year-round mentorship program that includes: (a) annual research and writing retreats (including a 5-day Fall Immersion Research Training Institute; a 5-day Spring writing retreat; a 1-day AIAN Substance Abuse Research Summit and grant development workshop at the NIDA AIAN national meeting or a selected national scientific conference; (b) year-round multidisciplinary learning and research experience opportunities (4 quarterly webinars/seminars; funding for on-site Mentor shadowing opportunities; and support for attendance to national NIDA research meetings); (c) technical assistance (peer review for grant development and submission; statistical, editorial and technical assistance for developing grant applications and manuscript preparation); (d) seed funding ($22,000 for postdoctoral/early career scientists and $10,800 for doctoral students to conduct pilot studies, conference travel, and travel to meet with mentors and mentorship teams); and (e) network development (via mentor networks and website). By the end of the program, Fellows will have designed and implemented a pilot study, published SAA-related articles; presented at a SAA-related conference, and developed or submitted a NIH SAA-related grant proposal.